case study discussions on the nurse’s role in caring for ... and case study ... if there is...

10/26/2015

1

Case Study Discussions on the Nurse’s Role in Caring

for Patients With Hematologic Malignancies

Welcome and Overview

Lauren Berger, MPHSenior Director, Professional Education and Engagement

The Leukemia & Lymphoma Society

Case Study Discussions on the Nurse’s Role in Caring for Patients With Hematologic Malignancies

www.LLS.org/CE2

10/26/2015

2

Faculty Disclosures

• Emily Bennett, RN, BSN

• Beth Finley, RN, BSNc, OCN

• Lynn Rich, ANP-BC,OCN

Have no affiliations with commercial interests to disclose

3

Acute Promyelocytic Leukemia (APL) Overview and Case Study

Emily Bennett, RN, BSN Nurse Navigator

Winship Cancer InstituteEmory University

Atlanta, GA


4

10/26/2015

3

Outline

• Leukemias and outcomes

• History of APL

• Epidemiology

• Treatment and outcomes in large trials

• What happens outside of a trial

• High mortality outside of a trial

• What is involved in our co-management

5

Leukemias and Outcomes

Chronic Leukemias• Chronic myelogenous

leukemia (CML) – Imatinib (Gleevec) ≥90%

survival• Chronic lymphocytic

leukemia (CLL)– Indolent disease in the elderly– Wide array of treatments is

available

Acute Leukemias• Acute lymphoblastic

leukemia (ALL) – Generally pediatric disease

with ≥80% cure rate– Cure rates are approximately

40%–50% in adults• Acute myelogenous

leukemia (AML)– Generally seen in older

patients– M1 to M7: 50% cure rate

across the spectrum• M3 – Acute promyelocytic

leukemia (APL)

6

10/26/2015

4

APL Therapy – History

7

ATO, arsenic trioxide; ATRA, all-trans retinoic acid; CT, chemotherapy; GO, gemtuzumab ozogamicin; RA, retinoic acid.Chen Y, et al. Cancer. 2012;118(23):5811–5818.Nowak D, et al. Blood. 2009;113(16):3655–3665.

First description:Hyperacute fatal illness

associated with hemorrhagic syndrome

First description:Hyperacute fatal illness

associated with hemorrhagic syndrome

Daunorubicin in APL

Daunorubicin in APL

In vivo leukemic cell

differentiation

In vivo leukemic cell

differentiation

Discovery t(15;17) in APL

Discovery t(15;17) in APL

ATRA therapyATRA therapy

Differentiation of APL cells with

RA

Differentiation of APL cells with

RA

ATRA + CTATRA + CT

ATO in relapseATO in relapse

ATO frontline

ATO frontline

ATRA + ATO ± GO

ATRA + ATO ± GO

7

APL Diagnosis – Pathology

• Pancytopenia – low counts

• DIC common

• Bruising – typical complaint

• Bleeding – quite serious

‒ Serious bleeds with normal lab findings

• CNS bleeds – common

‒ Most likely reason for patient deaths due to bleeding

8CNS, central nervous system; DIC, disseminated intravascular coagulation.

Sanz MA, et al. Blood. 2009;113(9):1875–1891.. 8

10/26/2015

5

APL – Epidemiology

• APL is an uncommon disease with approximately 1000 new cases per year in the US

• Rare below 10 years of age

• Most common between the ages of 20 and 60 years

• Historically, this is the first disease for which targeted treatment was developed

• Highly effective and curable treatments

– All-trans retinoic acid (ATRA), arsenic trioxide (ATO), and anthracyclines

9

APL Treatment and Outcomes in Large Trials


10

10/26/2015

6

APL Survival in Large Cooperative Group Trials

1111OS, overall survival.

Australasian APML4 (adding ATO to ATRA/chemo)

12CI, confidence interval; DFS, disease-free survival; EFS, event-free survival; HR, hazard ratio; OS, overall survival. 12

10/26/2015

7

ATRA/ATO vs ATRA/Chemotherapy

1313

EFS

prob

abili

tyC

umul

ativ

e in

cide

nce

of re

laps

e

What Happens Outside of a Trial


14

10/26/2015

8

Case Study – Real-World Patient

• 56-year-old female; Jehovah’s Witness

• Current diagnosis of flu, normal CBC (early December), treated with Tamiflu; DVT (late December), repeat CBC showing pancytopenia

• Subsequent work-up resulted in a diagnosis of APL

• Refused blood transfusions, so she was supported with cryoprecipitate, Aranesp, Procrit and

G-CSF, which was approved by her congregation

CBC, complete blood count; DVT, deep vein thrombosis; G-CSF, granulocyte colony-stimulating factor. 15

Population-Wide Survival in the US

• Survival of 90% in multicenter trials is not a reflection of the outcome in the general population. Death rate of 5% to 10% is an underestimate

• Recent analysis of US SEER data from 2000–2008 by investigators from MD Anderson showed 71% survival at 1 year and 64% at 5 years

• Current trials that are changing sequence, adding new drugs, and/or withholding maintenance will only have a minimal effect on the survival

• Biggest impact will be made by decreasing early deaths

16Chen Y, et al. Cancer. 2012;118(23):5811–5818. 16

10/26/2015

9

SEER Data (1975–2008)

Chen Y, et al. Cancer. 2012;118(23):5811–5818. 17

Survival Data From SEER Registries

18

0

10

20

30

40

50

60

70

80

90

Sfo SJ LA CA CT HI ATL GA IA KY Lo DTW NJ NM UT Seat

1 yr Survival

2005‐2011 (post atra)

Expected ~95%

18

10/26/2015

10

Early Deaths in APL (Days 1 to 30)

1919

Why Is There High Mortality Outside of a Trial?


20

10/26/2015

11

Possible Reasons

• Selection bias: possible reason • Delayed treatment

– Delay in ATRA treatment is commonly cited but not the case

• Decreased supportive care?– Probably the biggest reason

• Prior to ATRA, early deaths in GIMEMA were <10• They have a network of treatment centers that follow

written guidelines• MD Anderson had 5/44 early deaths in their clinical trial

but 9/40 after the trial closed

2121

Can We Do Something Different?

2222Image used with permission from Bearman Cartoons.

10/26/2015

12

Strategy (at GRU)

• Developed a simple 1.5-page treatment algorithm

• Quick diagnosis

• Ad hoc meeting and treatment planning

• Rapid initiation of therapy

• Aggressive management of coagulopathy

• Prevention of differentiation syndrome; early recognition and management of ATRA syndrome

• Prophylaxis and aggressive treatment of infections

• Implemented in 2010

2323

Methods Used to Decrease Early Deaths

• Reviewed the literature

• Reviewed all patient charts

• Attended national meetings and talked to experts

• Attended the International APL meeting in Rome

• Obtained an external consultant to review our death charts

• Identified the three main causes of death in the first month: BLEEDING, DIFFERENTIATION SYNDROME AND INFECTION

• Implemented a proactive, simple program to decrease early deaths—at a point when the rest of the country did not recognize this as a problem

2424

10/26/2015

13

What Is Involved in Our Co-Management

25


Treatment Outside Our Center

• Co-manage patients

• Text or email has worked very well

• Discuss day-to-day care in case they are more complicated

• Idea is to get them through induction

2626

10/26/2015

14

APL – Workup

• Quick diagnosis

• Rapid initiation of therapy

• Aggressive management of coagulopathy

• Prevention of differentiation syndrome; early recognition and management of ATRA syndrome

• Prophylaxis and aggressive treatment of infections (APL IS A MEDICAL EMERGENCY. TREATMENT WITH ATRA SHOULD BE STARTED ASAP)

• Labs, BMBX, ECHO, PICC (no invasive procedures)

BMBX, bone marrow biopsy; ECHO, echocardiogram; PICC, peripherally inserted central catheter. 27

Supportive Care

• Tumor lysis prophylaxis

• Antibacterial prophylaxis – Levofloxacin 500 mg QD

• Antifungal prophylaxis – Voriconazole 200 mg PO BID or posaconazole 200 mg PO TID

• Antiviral prophylaxis – Acyclovir 400 mg BID

• Keep hemoglobin in the 8 range

• APL IS A MEDICAL EMERGENCY. TREATMENT WITH ATRA SHOULD BE STARTED ASAP

BID, twice daily; PO, orally; QD, daily; TID, three times daily. 28

10/26/2015

15

Treatment of Coagulopathy

• Coagulopathy is a major problem. Procoagulants released by leukemia cells and fibrinolysis

• Intracranial, pulmonary and GI bleeding

• Treatment with ATRA should start ASAP

• Keep platelets above 50,000

• Keep fibrinogen above 150

• If there is clinical evidence of bleeding, give FFP twice a day as you are starting ATRA and chemotherapy until bleeding resolves

• After all clinical and lab coagulopathy resolves, blood product support is like any other leukemia

29FFP, fresh frozen plasma; GI, gastrointestinal. 29

Differentiation Syndrome

• Dyspnea, unexplained fever, weight gain, ARF, CHF, pleuropericardial effusions and interstitial pulmonary infiltrates

• Meticulous monitoring of intake and output. Daily weights

• Keep I/O matched (SHOULD BE METICULOUS)

• Diuretics should be used if there is evidence of fluid retention and weight gain

• Dexamethasone 10 mg BID should be started as soon as symptoms are noted

• In patients with a WBC >10,000, dexamethasone 10 mg BID could be started before initiating ATRA

• Temporary discontinuation of ATRA or ATO is indicated only in case of severe APL differentiation syndrome

30ARF, acute renal failure; BID, twice daily; CHF, congestive heart failure; WBC, white blood count. 30

10/26/2015

16

Treatment: AIDA Regimen Example

• Induction – Low-risk patients

• WBC <10,000 and platelet count >40,000

• GIMEMA protocol. ATRA on day 1 followed by idarubicin 12 mg/m2 on days 2, 4, 6 and 8 (AIDA)

– Intermediate-risk and high-risk patients• WBC >10,000 and platelet count <40,000

• ATRA to be started as soon as diagnosis is suspected

• Idarubicin to be started on the same day and given per the GIMEMA protocol on days 1, 3, 5 and 7. Even if genetic results are unavailable, it is reasonable to give anthracycline

• Older patients (individualized)

31WBC, white blood count.

Older Patients With APL

• Need to individualize

• Maybe begin with single-agent ATRA

• Dose reduction of ATO

• Meticulous supportive care

3232

10/26/2015

17

Nursing Considerations

• Meticulous monitoring of patient during the first 10 days during which 70% of deaths occur

• Primary goal is to decrease early deaths within the first month; three main causes of death in the first month: BLEEDING, DIFFERENTIATION SYNDROME AND INFECTION

• Rapid initiation of therapy • Aggressive management of coagulopathy• “Normal” laboratory values can still cause bleeding• Prevention or early recognition and management of ATRA

syndrome• Prophylaxis and aggressive treatment of infections• Outpatient consolidation, provide calendars, dialogue with

patient and family

33

Consolidation and Maintenance

• Generally depends on induction protocol

• If you pick a regimen, try to stick with the same follow-up treatments

‒ Two to three cycles of anthracycline-based consolidation, given along with ATRA

‒ ATO-based consolidation

• After completion of consolidation, a bone marrow evaluation should be done to demonstrate molecular remission

‒ If molecular remission is achieved, maintenance with 1–2 years of oral ATRA + MTX and 6MP may be beneficial

6MP, 6-mercaptopurine; MTX, methotrexate. 34

10/26/2015

18

Algorithm

35

Work Up CBC, CMP, and DIC Panel to include Fibrinogen, D-Dimers, PT and PTT twice a day until all laboratory and clinical coagulopathy is completely resolved. Echocardiogram. Bone Marrow Examination. Aspirate, Biopsy, Flow cytometry, Cytogenetics, FISH for PML-RAR alpha and PML-RAR alpha by PCR. Tumor banking if available. Baseline Chest X-ray PICC Line. Do NOT attempt to put central lines or perform other surgically invasive procedures such as Bronchoscopy or Spinal Tap. DAY 14 Marrow is not necessary.

Supportive care Tumor Lysis prophylaxis. Antibiotic Prophylaxis with Levofloxacin 500 mg po qd or similar antibiotic. Antifungal prophylaxis with Posaconazole 200 mg po tid, Voriconazole 200 mg po bid or another agent with similar efficacy Anti-viral prophylaxis with Acyclovir 400 po bid or Valacyclovir 1000 mg PO daily Red Cell transfusion is similar to other Leukemia Induction and suggested to transfuse at or below 7gm/dl. APL IS A MEDICAL EMERGENCY. TREATMENT WITH ATRA SHOULD BE STARTED ASAP.

Coagulopathy Intracranial, Pulmonary and GI Hemorrhage. Risk of Bleeding is worse in patients with Active Bleeding, Hypofibrinogenemia, Increased levels of D-Dimers, prolonged PT and PTT, increased WBC, increased Peripheral Blasts, Renal Failure and poor PS

Treatment with ATRA should start ASAP Keep platelets above 50,000 If there is clinical evidence of bleeding at presentation from needle sticks, Bone Marrow Biopsy sites, give 4 units of FFP as you are starting the ATRA and Chemotherapy. Continue FFP support twice a day until

clinical bleeding resolves. Keep fibrinogen above 150. Use cryoprecipitate if needed After all clinical and laboratory coagulopathy has resolved, the guidelines for blood product support are similar to management of other leukemias.

Differentiation

Syndrome Meticulous monitoring of Intake and Output. Daily weights Keep I/O matched (SHOULD BE METICULOUS). Diuretics should be used if clinically there is evidence of fluid retention and weight gain. Dexamethasone at 10 mg BID should be started as soon as symptoms are noted. In patients with a WBC >10,000, Dexamethasone 10 mg bid could be started before initiating ATRA Temporary discontinuation of ATRA or Arsenic Trioxide (ATO) is indicated only in case of severe APL DS. Dexamethasone should be maintained until complete disappearance of symptoms and ATRA or ATO should be restarted. Dexamethasone should be stopped 3 days after all DS symptoms have resolved.

Anthracycline based Induction INDUCTION OF LOW RISK PATEINTS (WBC <10,000/ml and Platelets >40,000/ml) GIMEMA protocol. ATRA on Day 1 followed by idarubicin 12 mg/m2 on Days 2, 4, 6 and 8.INDUCTION OF INTERMEDIATE RISK AND HIGH RISK PATIENTS(WBC> 10,000 and Platelet count <40,000) Idarubicin to be started on the same day and given per the GIMEMA protocol on days 1, 3, 5 and 7. Even if the genetic results are not available, it is reasonable to give the anthracycline. Aggressive management of coagulopathy.

Arsenic trioxide based induction Can be considered in the following patient groupsa) Low and intermediate risk patients (WBC < 10,000/ml)b) Age >70 c) Not candidates for conventional chemotherapy for any reason. Should be restricted to patients with confirmed PML-RAR alpha. ATRA at 45 mg/m2 in divided doses twice a day along with Arsenic at 0.15 mg/kg daily, both continued till complete hematologic remission. Watch for differentiation syndrome. Follow for prolongation of QT interval. Keep Mg above 2.0 and K above 4.0. Follow LFTs and for grade 2 to 4 Liver Dysfunction, HOLD Arsenic.

Hydroxyurea use for Leukocytosis:

NO LEUCOPHERESIS

WBC 5 - 10k – Hydroxyurea 500 mg q day WBC 10 – 15k Hydroxyurea 500mg BID WBC 15 – 20k – Hydroxyurea 500mg TID WBC 20 – 50k – Hydroxyurea 500 mg QID WBC > 50k – Hydroxyurea 1000 mg QID Could also give a dose or two of Idarubicin 12mg/m2 if the Leukocytosis does not resolve or DS does not resolve in spite of using Dexamethasone. 35

Experience in Other Diseases

• STEMI – Shorter door-to-balloon time improves survival

• In stroke patients, administration of TPA within 3 to 4.5 hours of symptom onset improves survival

• THE GOAL IS TO STREAMLINE THE PROCESS

36

STEMI, ST-segment elevation myocardial infarction; TPA, tissue plasminogen activator.McNamara RL, et al. J Am Coll Cardiol. 2006;47(11):2180–2186.Hacke W, et al. N Engl J Med. 2008;359(13):1317–1329. 36

10/26/2015

19

Strategy to Decrease Early Deaths at Main and Affiliate Sites

• Primary goal: prospectively assess 30-day mortality; Secondary goal: collect survival date

• Widespread education of hematologists, oncologists and nursing staff about early deaths and the need for rapid diagnosis and treatment

• At main sites: Ad hoc meeting at patients’ admission with physicians, residents and nurses and rapid initiation of therapy

• At affiliate sites: An Investigator will help manage patients at affiliate sites using the same algorithm as outlined in the strategy we have used so far

• Decrease induction mortality to 5%–8%

3737

Survival Pre- and Post-Algorithm

38

10/26/2015

20

Planned Coverage on New NCI-ECOG Trial

Cover entire population of ~15 m

Half the population of AL: ~2.5 m

Half the population of FL: ~10 mDr. James Foran

Half the population of MN: ~2.5 m Sub I: Dr. Mark Litzow

Half of NC and TN: ~8 m

Half of IL: ~5 m Dr. Altman

Parts of NY and PA: ~10 mDr. TallmanDr. Luger

States with Investigators:ECOG centers:

39ECOG, Eastern Cooperative Oncology Group; NCI, National Cancer Institute.

Resources

• Difficult obtaining patient assistance for drug• Very expensive • No patient assistance programs for drug cost• The Leukemia & Lymphoma Society’s

Information Resource Center (refer to support and financial assistance programs)

• Limited pharmaceutical assistance program• Social work (prescription plans, financial,

transportation)

40

10/26/2015

21

Conclusions

• Early deaths can and SHOULD be prevented in APL

• This concept was already validated in Latin America—Brazil, Chile,

Uruguay and Mexico. Decreased early deaths from 32% to 15%

• Expedite diagnosis and treatment

• Proactively manage the three main causes of death

• Treating oncologists may be unaware of the problem

• Minimize complications from the presence of thrombocytopenia/

bleeding/infection

• APL is a curable disease amongst the leukemias

Rego EM, et al. Blood. 2013;121(11):1935–1943. 41

Thank You

42


10/26/2015

22

Chronic Lymphocytic Leukemia (CLL)Overview and Case Study

Lynn Rich, ANP-BC, OCNNurse Practitioner

JP Wilmot Cancer InstituteUniversity of Rochester

Rochester, NY


43

Outline

• Define disease • Describe how CLL/SLL is different from

leukemia: acute vs chronic leukemia• Natural history of disease• Epidemiology• Rai staging • Goal of treatment• Case study

44

10/26/2015

23

What Is CLL?

• Chronic lymphocytic leukemia (CLL) is a cancer of the lymphocytes that normally work as immune cells to protect against infections

CLL Cell

Red Blood Cells

Image courtesy of JP Wilmot Cancer Institute; Chronic Lymphocytic Leukemia (CLL) Booklet. 45

Smudge Cell

CLL

• CLL is caused when a single B lymphocyte becomes abnormal because of damage (mutation) to its DNA

• Once this occurs, the body no longer controls this cell, so it continues to divide and lives longer than it should

• This abnormal cell becomes CLL

46

10/26/2015

24

CLL vs SLL

• Small lymphocytic lymphoma (SLL) is a variant of the disease in which there are not a lot of abnormal lymphocytes in the blood

• World Health Organization (WHO) classification considers the two diseases to be identical—one disease at different stages

47

CLL – Lymphocyte dysfunction is in the bone marrowSLL – There is more lymph node and lymphoid tissue involvement (vs bone marrow) 48

10/26/2015

25

CLL vs Acute Leukemia

• Chronic leukemias usually progress slowly, and there are a greater number of mature cells that can generally carry out normal function

• Acute leukemias are diseases that progress rapidly and affect cells that are not fully developed

49

Image courtesy of JP Wilmot Cancer Institute; Chronic Lymphocytic Leukemia (CLL) Booklet. 50

10/26/2015

26

How Is CLL Diagnosed?

• Often found on random complete blood count (CBC) by primary

• Notice an elevated white blood count (WBC), specifically elevated lymphocytes

51

Case Study: Maria S.

• 76-year-old widowed female in reasonably good heath; no other comorbidities

• Retired bus driver • Lived in upstate NY • March 2011: went to primary

– Fatigue; “just did not seem right”

• Noted to have elevated WBC: 30 (normal 4–10)• Was sent to local community oncologist

52

10/26/2015

27

Normal CBC

• WBC – normal 4–10• Differential:

– Neutrophils: 1.8–5.4 K/uL (ANC)– Lymphocytes: 1.3–3.6 K/uL (ALC)– Monocytes: 0.3–3.6 K/uL– Eosinophils: 0–0.5 K/uLALC >5.0 – criteria to meet CLL (lymphocytosis)

must show clonality on peripheral blood

• 2008 update of the National Cancer Institute guidelines

ALC, absolute lymphocyte count; ANC, absolute neutrophil count. 53

Natural History of CLL

• Considered indolent (slow-growing) in nature

• Can watch for 5–10 years without intervening

• Life expectancy could be 10–20 years• However, some patients need treatment

quickly and aggressively• How can we tell?

54

10/26/2015

28

Further Staging: FISH(fluorescent in situ hybridization)

• 13 q = favorable (17-year median OS)• Trisomy 12 and 11 q = less favorable

(9–11 years)• 17p – associated with mutated TP53

– Poor response rate– Short duration of response with standard

treatment– Most unfavorable prognosis (7-year median OS)

Example: Combined 11q + 17p = more unfavorable

OS, overall survival.

Wormsley SB, et al. Blood. 1990;76(1):123–130. 55

Case Study: CBC at Presentation

• WBC: 30• ALC: 6.0• What else is needed when initially diagnosed?• Obtain CT staging scans

• Assess for organomegaly, extent of lymphadenopathy• Patient did not have

• Obtain bone marrow biopsy• Assess for evidence of disease; if so, how much?• Patient had 85% CLL in bone marrow

ALC, absolute lymphocyte count; CT, computed tomography. 56

10/26/2015

29

Epidemiology

• In 2013, an estimated 119,386 people in the United States were living with CLL

• 15,720 people were expected to be diagnosed with CLL in 2014

The Leukemia & Lymphoma Society. Chronic Lymphocytic Leukemia. 2014.

Total CLL

CLL 2014

Total CLL expected in 2014: 120,000New CLL cases in 2014: 15,720

57

Epidemiology (cont’d)

• The most common type of leukemia in Western countries

• Considered disease of the elderly

• Median age at diagnosis is 70 years

• However, not unusual to make this diagnosis in younger individuals from 30–39 years of age

58

10/26/2015

30

Risk Stage Description

Low 0 Lymphocytosis in blood or bone marrow

Intermediate

I Lymphocytosis + enlarged lymph nodes

II Lymphocytosis + enlarged liver or spleen with/without lymphadenopathy

High

III Lymphocytosis + anemia (Hgb <11), with/without enlarged liver, spleen or lymph nodes

IV Lymphocytosis + thrombocytopenia (<100) with/without anemia, enlarged liver, spleen or lymph nodes

Hgb, hemoglobin.International Workshop on CLL. Ann Intern Med. 1989;110(3):236–238.

Modified Rai Clinical Staging for CLL

59

Case Study: Patient

• March 2011: Presented with intermediate Rai stage • August 2011: Rituximab• October 2011: Bendamustine/Rituximab• January 2012: Increasing WBC, enlarging organomegaly• Responded poorly: ALC from 30 to 100

• Referral made to CLL specialist at University of Rochester: clinical trial options

ALC, absolute lymphocyte count. 60

10/26/2015

31

61

Ibrutinib: BTK

• 140-mg oral tablet:– CLL dose is 480 mg daily

– FDA approved in 2014

62

10/26/2015

32

Case Study: Treatment Course

0

50

100

150

200

250

300

Lenalidomiderituximab

IdelalisibGS-9973

Ibrutinib

• Significant lymphocytosis: WBC spikes within first month of treatment• Usually takes 2–3 months for WBC to return to normal

63

Other Nursing Considerations

• Reasonably well tolerated – Not known to cause nausea

• Important side effect profile• Bleeding and bruising

– Should be considered “blood-thinning agent”– Hold 5–7 days prior to invasive procedure; restart

7 days after

• Known to cause some diarrhea– Typically can treat through; expect 1–2 bouts per day

for first week. Patients usually recover quickly

64

10/26/2015

33

Duration of Response

• Patients attain a complete remission

• How long will this last?

• Patients have been in remission for up to 3 years to date

65

Survivorship Issues

• Social workers and nursing: necessary to offer extensive emotional support

• During remission: often feel satisfied with response, but fearful of time because they wonder how long remission will last

• Secondly, ibrutinib is an expensive drug – Often need social work support to assist with financial

assistance– Often turn to The Leukemia & Lymphoma Society for

assistance with information gathering, as well as financial support

66

10/26/2015

34

67

Audience Discussion QuestionMany oncologists consider any patient diagnosed with cancer a survivor, what makes a CLL survivor

different? What special considerations are required in this population?


Multiple Myeloma Overview and Case Study

Beth Finley-Oliver, RN, BSNc, OCNPrimary Nurse

Moffitt Cancer Center

Tampa, FL


68This presentation was recorded in the studio following the ONS symposium

10/26/2015

35

Outline

• Understanding the Disease– Staging systems– Response criteria

• Case Study• Treatment Strategy

– Transplant vs non-transplant candidate• Treatment Options

– Newly diagnosed• Nursing Considerations for Myeloma Patients

– Bone health– Kidney health– Anemia– Preventing complications

• Multidisciplinary Team– Social worker– Physical and occupational therapist

• Financial assistance69

What Is Myeloma?

Cancer of plasma cells• An uncontrolled growth of plasma cells

Myeloma begins in the bone marrow• Spongy tissue found in the center of bones

Bone marrow

Marrow cells from apatient with myeloma

70

10/26/2015

36

“M-spike”– Monoclonal Paraproteins

Myeloma Cell- Produce Antibodies

Antibody- Heavy and light chain

components

Intact Ig Myeloma~80% MM

Eg, IgG kappa

Light Chain Myeloma

~15%–20% MMEg, kappa

Non-Secretory/Oligosecretory

~0.5%–5% MMEg, kappa

Heavy Chain- IgG >IgA >>IgD &

IgE >> IgM

Light Chain- Kappa (κ) > lambda (λ)

Ig, immunoglobulin; MM, multiple myeloma.71

Diagnosing Myeloma

72

10/26/2015

37

Diagnosis: “CRAB” Criteria

Presentation:• Hypercalcemia (C)• Renal Failure (R)• Anemia (A)

– Fatigue

• Fractures (B)– Bone pain

• Infections (I)

Durie BG, et al. Leukemia. 2006;20(9):1467–1473.73

Ca++

Lytic Lesions

74

10/26/2015

38

Durie-Salmon Staging System

Ig, immunoglobulin.

Durie BG, et al. Cancer. 1975;36(3):842–854.

Stage I

All of the following:Hemoglobin >10 g/dLSerum calcium normal (<12 mg/dL)Bone X-ray normal or solitary bone plasmacytoma onlyLow M-protein production (IgG <5 g/dL; IgA <3 g/dL)Bence-Jones protein <4 g/24 hours

One or more of the following:Hemoglobin <8.5 g/dLSerum calcium >12 mg/dLAdvanced lytic bone lesionsHigh M-protein production rates (IgG >7 g/dL; IgA >5 g/dL; Bence-Jones protein >12 g/24 hours)

Stage III

Fitting neither stage I nor IIIStage II

75

Durie-Salmon sub classifications (either A or B)A: Relatively normal renal function (serum creatinine value <2.0 mg/dL)B: Abnormal renal function (serum creatinine value =2.0 mg/dL)

Stage II

Factors: Beta-2 microglobulin <3.5 mg/LAlbumin <3.5 g/dL or

Beta-2 microglobulin ≥3.5–<5.5 mg/L

Stage III

Factors: Beta-2 microglobulin ≥5.5 mg/L

Better Response to Therapy

Stage I

Factors: Beta-2 microglobulin <3.5 mg/LAlbumin ≥3.5 g/dL

Lesser Response to Therapy

LessFavorable Prognosis

MostFavorable Prognosis

International Staging System (ISS)

Greipp PR, et al. J Clin Oncol. 2005;23(15):3412–3420. 76

10/26/2015

39

MM Risk Stratification

High Risk (25%) Standard or Good Risk (75%)

t(4;14) by FISH

t(14;16) or t(14;20) by FISH

Deletion 17q13 by FISH

Deletion 13 by metaphase analysis

Aneuploidy by metaphase analysis

Plasma cell labeling index >3.0

Beta-2 microglobulin >5.5

High-risk MyPRS™

Hyperdiploidy

t(11;14) by FISH

t(6;14) by FISH

Βeta-2 microglobulin <5.5

Labeling index <2.0

FISH, fluorescence in situ hybridization; MM, multiple myeloma; MyPRS, Myeloma Prognostic Risk Signature.77

TreatmentTreatment Plan

Patient

Preference Cytogenetics

Overall Health Status

AgeMyeloma

Stage

Factors Influencing Treatment Choice

78The Leukemia & Lymphoma Society. Myeloma: A Guide for Patients and their Families. March 2005.

10/26/2015

40

Response Criteria

Response Type M ProteinPlasma Cells in Bone Marrow Other

Stringent complete response (sCR) None (blood/urine) No abnormal

plasma cellsNo free light chains

Complete response (CR) None (blood/urine) <5% Disappearance of soft tissue plasmacytoma

Very good partial response (VGPR) >90% reduction (blood) NA NA

Partial response (PR)>50% reduction in serum and >90% reduction in urine

NA>50% reduction in the size of soft tissue plasmacytoma

Minimal response (MR)25%–49% reduction in blood and reduction of 50%–89% in urine

NA25%–49% reduction in the size of soft tissue plasmacytoma

Stable disease (SD) Does not meet criteria for response or progressive disease

Progressive disease (PD) >25% increase (blood or urine) >10%

New bone lesions, soft tissue plasmacytoma, high calcium levels

Durie BG, et al. Leukemia. 2006;20(9):1467–1473.79

Case Study

• 61-year-old male

• Presentation– SPEP: 3.6

– IgG: 6791

– Serum free light chain -Lambda: 89.56

– Beta-2 microglobulin: 2.3

– Albumin: 3.2 g/dL

– Calcium: 8.2 mg/dL

– Creatinine: 0.8 mg/dL

– Hemoglobin: 9.3 g/dL

– UPEP: 156 mg/24 hours

• BMBX 70%–80% plasma cells

• Survey + lytic lesions– Skull

– 8th rib fracture

– FISH results• Hyperdiploidy

• 13q deletion

• t(11;14)

– ISS II

– Durie-Salmon Stage 2A

BMBX, bone marrow biopsy; FISH, fluorescence in situ hybridization; Ig, immunoglobulin; SPEP, serum protein electrophoresis; UPEP, urine protein electrophoresis.

80

10/26/2015

41

Treatment Options for Transplant-Eligible Patient

• Transplant• Avoid melphalan

– RVD• Lenalidomide 25 mg,

days 1–14

• Bortezomib 1.3 mg/m2, days 1, 4, 8, and 11

• Dexamethasone 20 mg PO, days 1, 2, 4, 5, 8, 9, 11, and 12

– VDC• Bortezomib 1.3 mg/m2,

days 1, 4, 8, and 11

• Cyclophosphamide 500 mg PO, days 1, 8, and 15

• Dexamethasone 20 mg PO, days 1, 2, 4, 5, 8, 9, 11, and 12

Bisphosphonate Monthly

RVD, lenalidomide, bortezomib, and dexamethasone; VDC, bortezomib, dexamethasone, and cyclophosphamide.81

Response: VGPR

0

0.51

1.5

2

2.53

3.5

4

12/11

/201

2

01/11

/201

3

02/04

/201

3

02/22

/201

3

03/15

/201

3

04/05

/201

3

04/26

/201

3

Date

0

10002000

3000

4000

50006000

7000

8000

M protein

IgG

BMT evaluation:

PR, 2 more cycles

BMT, bone marrow transplant; Ig, immunoglobulin.82

10/26/2015

42

Disease Course

0

0.51

1.5

2

2.53

3.5

4

12/11

/201

2

01/11

/201

3

02/04

/201

3

02/22

/201

3

03/15

/201

3

04/05

/201

3

04/26

/201

3

05/13

/201

3

09/09

/201

3

02/20

/201

4

07/01

/201

4

01/06

/201

5

03/03

/201

5

Date

M s

pik

e (g

/dL

)

0

10002000

3000

4000

50006000

7000

8000

IgG

(m

g/d

L)

M protein

IgG

High-dose melphalan and autologous

transplant 6/5/2013

PD

Ig, immunoglobulin.83

Nursing Considerations

84


10/26/2015

43

Managing Side Effects

85


Immunomodulatory Drugs (IMiDs)

Thalidomide Lenalidomide Pomalidomide

Myelosuppression Minimal Yes Yes

VTE Yes Yes Yes

GI Constipation Diarrhea Diarrhea

Rash Yes Yes Yes

Sedation Yes No No

Neuropathy Yes No No

Teratogens!

GI, gastrointestinal; VTE, venous thromboembolism.86

10/26/2015

44

Proteasome Inhibitors

Bortezomib Carfilzomib

Schedule Days 1, 4, 8, and 11 every 21 days

Days 1, 2, 8, 9, 15, and 16 every 28 days

Modes of administration IV/SC IV

Myelosuppression/ thrombocytopenia

Yes Yes

Neuropathy Yes No

Zoster Yes Yes

Dyspnea No Yes

Fatigue Yes Yes

GI Yes No

Cardiac/pulmonary (RARE) No Yes

GI, gastrointestinal; IV, intravenous; SC, subcutaneous. 87

Steroids (Dexamethasone/Prednisone)

• Mood Swings

• Insomnia

• Irritability

• Hyperactivity

• Edema

• Flushing

• Fatigue

• Blurry vision

• Cataracts

• Dyspepsia– PPI

• Muscle atrophy

• Hyperglycemia

• Acne

• Muscle cramping

• Taste changes

• Ulcer

• Weight gain

• Hair loss

PPI, proton pump inhibitor.

Faiman B, et al. Clin J Oncol Nurs. 2008;12(3):53–62.88

10/26/2015

45

Nurse’s Role

• Education and support– Oral adherence to complex regimens

• Improving quality of life by helping to manage side effects

• Navigating patients and their caregivers throughout the disease process

89

Bone Health

• Bisphosphonates– Avoid invasive dental procedures

– Prevent pathological fractures• Orthopedist

• Neurosurgeon

• Pain control– Avoid NSAIDs

– Narcotic education

NSAID, non-steroidal anti-inflammatory drugs.

Miceli TS, et al. Clin J Oncol Nurs. 2011;15(4):9–23.90

10/26/2015

46

Renal Health

• Cast nephropathy (myeloma kidney)• Hypercalcemia

– Aggressive hydration and treatment• Dehydration

– IV fluids• NSAIDS• IV contrast• Aminoglycoside antibiotics

– Gentamycin, tobramycin, etc.• Bisphosphonates

IV, intravenous; NSAID, non-steroidal anti-inflammatory drugs.

Faiman B, et al. Clin J Oncol Nurs. 2011;15(4):66–76.91

Anemia

• Due to disease or treatment

• Supportive care

– Erythropoietin-stimulating agents

• Epoetin alfa

• Darbepoetin alfa

– PRBC transfusions

– Fatigue • Treatment

• Disease

• Physical therapyPRBC, packed red blood cell.

92

10/26/2015

47

Safety and Mobility

• Exercise– Physical/Occupational therapy

• Nutrition and hydration– Consult from nutritionist

• Psychosocial well-being– Support system– Fatigue– Sleep disturbances– Anxiety– Depression

Rome SI, et al. Clin J Oncol Nurs. 2011;15(suppl):41–52.93

Multidisciplinary Team Approach

• Social workers– Financial assistance programs

• Non-profit organizations– The Leukemia & Lymphoma Society– Chronic Disease Fund– Patient Network Access

• Pharmaceutical companies• Physical and occupational therapists• Dietician• Pharmacist• Dentist

94

10/26/2015

48

Summary

• Multiple myeloma is most often a chronic and complex disease

• Treatment decisions are individualized to the patient

• Managing side effects helps patients maintain quality of life

• A multidisciplinary team approach helps support patients and caregivers

95

Thank You

96


10/26/2015

49

Follicular Lymphoma Overview and Case Study

Lynn Rich, ANP-BC, OCNNurse Practitioner

JP Wilmot Cancer InstituteUniversity of Rochester

Rochester, NY


97This presentation was recorded in the studio following the ONS symposium

Outline

• Define disease• Epidemiology• Natural history of disease

– Indolent vs curable• Approved treatment options

– Rituxan maintenance vs observation• Use of idelalisib • Communication strategies: support of social

workers• Resources: survivorship challenges

98

10/26/2015

50

Lymphoma

General name given to a group of cancers that affect the lymphatic system• Includes:

– Lymph nodes – Plasma cells– Spleen– Lymphatic vessels– Bone marrow – Immunoglobulins

• Immune system helps protect against disease and infection

The Leukemia & Lymphoma Society. Non-Hodgkin Lymphoma. 2013.

Spleen

Lymphnodes

Bone Marrow

99

Lymphoma

Two distinct types: • Non-Hodgkin lymphoma (NHL)

– Approx. 50 different subtypes• Hodgkin lymphoma (HL)

– Approx. 5 different subtypes

100

10/26/2015

51

Follicular Lymphoma (FL)

• B-cell NHL (vs T/NK-cell NHL)

• Damage to DNA of one of the parent B cells causes a malignant transformation resulting in uncontrolled and exaggerated growth of the lymphocyte

101Image courtesy of JP Wilmot Cancer Institute; Chronic Lymphocytic Leukemia (CLL) Booklet.

Follicular Lymphoma (FL)

• 2nd most common subtype of NHL• Average age at diagnosis is 60 years• Indolent: slow-growing disease• Treatable, but not curable

– Impact of deciding treatment

The Leukemia & Lymphoma Society. Non-Hodgkin Lymphoma. 2013. 102

10/26/2015

52

NHL: Epidemiology

DLBCL

FL

T cell

Other B cell

Approximately 70,800 new cases of NHL in 2014

DLBCL, diffuse large B-cell lymphoma.The Leukemia & Lymphoma Society. Non-Hodgkin Lymphoma. 2013.

103

Case Study: MB

• 57-year-old married female– 3rd-grade elementary teacher – Symptom profile

• Abdominal fullness• Sweats• Fatigue• Lymphadenopathy

– Next step, stage?

104

10/26/2015

53

Ann Arbor Staging System

The Leukemia & Lymphoma Society. Non-Hodgkin Lymphoma. 2013.105

Case Study: MB

• Stage III– Bilateral axillary – small

– Abdominal – 10-cm mass

– Small inguinal node (groin node)

– Bone marrow negative (would have been stage IV)

106

10/26/2015

54

Treatment

• Watch and wait?

• Grade 1, 2, or 3?

107

Ready to Treat

• Criteria includes: – >3 sites of disease, 3 cm or

more

– 1 node measuring 7 cm

– Cytopenias – refractory thrombocytopenia disease

– Effusions

– Symptoms of disease, or B symptoms

– Threatened organ involvement

– Elevated LDH

LDH, lactate dehydrogenase.108

10/26/2015

55

Case Study: MB

• Treated with R-CHOP – completed 2007– Attained complete remission

• Consider maintenance with rituximab vs observation– Upfront vs consolidation– Things to consider:

• Expected response• Impact on overall survival• Quality of life• Financial impact

R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.109

Case Study: MB

• No maintenance rituximab

• Relapsed in 5/2008– Concerning?

• What we did: – Salvage RICE×2, then autologous

stem cell transplant

– Complete remission 9/2008

RICE, rituximab, ifosfamide, carboplatin, and etoposide.110

10/26/2015

56

Case Study: MB

• Relapsed 12/2014 – Essentially asymptomatic – mild abdominal

fullness

– However, CT of abdomen showed increased disease

• Is she ready for treatment?– What are the treatment options?

CT, computed tomography.111

Idelalisib – What Is It?

• PI3K inhibitor– Phosphoinositide 3-kinase delta

112

10/26/2015

57

Idelalisib

• Oral agent

• FDA approved in 2014

• Used for CLL/SLL or FL

• In relapsed setting

CLL/SLL, chronic lymphocytic leukemia/small lymphocytic lymphoma.113

Side Effect Profile

• Concern for pneumonitis or colitis– What to look for– When concerned– How to follow

• Concern for evolution of liver function abnormalities – What to look for – When concerned– How to follow

114

10/26/2015

58

Things to Consider

• Is this patient a good candidate?– Why wouldn’t she be?– Why would she be?

• Bring in social worker– Help to assess medical literacy (implications)– Help with financial assistance

• What are potential sources of assistance?

115

Communication Strategies

• Create a calendar with details– When to take pills, get blood drawn, etc.

• Dialogue with patient – Check in by phone

• At least weekly initially

• Consider MyChart®

• Eventually evolve to monthly visits, if tolerated

116

10/26/2015

59

What Happened to MB?

• Began idelalisib 150 mg BID

• Well tolerated

• Held after 2 months for elevated LFTs

• Update to date…

BID, twice daily; LFTs, liver function tests.117

Resources – Survivorship Issues

• The Leukemia & Lymphoma Society– www.LLS.org– Explore local chapter

support groups • YMCA – Exercise program

– Explain cancer survivor – Describe health and fitness

programs • Look for specific related survivor support groups

– www.LLS.org/survivorship

118

10/26/2015

60

Thank You


119

case study discussions on the nurse’s role in caring for ... and case study ... if there is...

Documents